F13A1 Gene Variant (V34L) and Residual Circulating FXIIIA Levels Predict Short- and Long-Term Mortality in Acute Myocardial Infarction after Coronary Angioplasty

Abstract

Factor XIIIA (FXIIIA) levels are independent predictors of early prognosis after acute myocardial infarction (AMI) and the Valine-to-Leucine (V34L) single nucleotide polymorphism (SNP) seems associated with lower AMI risk. Since the long-term AMI prognosis merits deeper investigation, we performed an observational study evaluating relationships between FXIIIA residual levels, cardiovascular risk-factors, and inherited genetic predispositions. FXIIIA V34L was genotyped in 333 AMI patients and a five-year follow-up was performed. FXIIIA levels assessed at day-zero (d0) and four days after AMI (d4), and conventional risk factors were analyzed, focusing on the development of major adverse cardiovascular events (MACE). FXIIIA assessed at d0 and d4 was also an independent MACE predictor in the long-term follow-up (FXIIIAd0, Odds Ratio (OR) = 3.02, 1.79–5.1, p = 0.013; FXIIIAd4, OR = 4.46, 2.33–8.55, p = 0.0001). FXIIIAd4 showed the strongest MACE association, suggesting that the FXIIIA protective role is maximized when high levels are maintained for longer time. Conversely, FXIIIA levels stratified by V34L predicted MACE at a lesser extent among L34-carriers (Hazard Risk (HR)VV34 = 3.89, 2.19–6.87, p = 0.000003; HRL34-carriers = 2.78, 1.39–5.57, p = 0.0039), and V34L did not predict all MACE, only multiple-MACE occurrence (p = 0.0087). Finally, in survival analysis, heart failure and death differed significantly from stroke and recurrent ischemia (p = 0.0013), with FXIIIA levels appreciably lower in the former (p = 0.05). Overall, genetically-determined FXIIIA levels have a significant long-term prognostic role, suggesting that a pharmacogenetics approach might help to select those AMI patients at risk of poor prognosis in the need of dedicated treatments.

Coagulation factor XIII activity predicts left ventricular remodelling after acute myocardial infarction

“…In the prospective study comprising 350 patients with MI, decrease of FXIIIa was associated with the development of heart failure and increased mortality risk. 14,15,29 Compared with our data, the patients in the study of Gemmati et al had lower baseline FXIIIa (95.0 ± 10.1%) and experienced stronger decline in FXIIIa within the first 3 to 4 days after MI (54.4 ± 6.5%); that is, relative decline of 40% in FXIII values from Day 0 to Day 4. The decline of FXIIIa was considerably less pronounced in our cohort, that is, from 118% to 109% (relative decline of 7.6%).…”

Changes in Adipose Tissue Distribution and Association between Uric Acid and Bone Health during Menopause Transition

“…Osteoporosis develops less often in men than in women and it has been considered for a long time as a "woman's disease", such as other complex diseases that have been stereotypically considered "men's diseases", creating a strong gender gap in patients' health care [32][33][34][35]. However, osteoporosis in men has now been recognized as a key health issue.…”

Sex/Gender-Specific Imbalance in CVD: Could Physical Activity Help to Improve Clinical Outcome Targeting CVD Molecular Mechanisms in Women?

“…We are aware that there are major limitations involved, particularly relating to the absence of well-established protocols to investigate and measure the biological effects of different physical exercise training in the context of CVD, along with the lack/scarcity of preclinical/clinical studies properly addressing the role of gender, other than the one of sex. Nonetheless, we believe that the focus of the present review in addressing a potential sex/gender-specific approach to preventing/managing CVD in women, which is at a disadvantage in the long term due to the clinical standard care, is of great relevance and may be of inspiration for new and innovative research in the field [1,3,8].…”

“…Of particular relevance is the issue of heart failure, which is expected to double each decade of life and to grow significantly in the whole population due to the dramatic increasing trend of population aging, particularly in the developed countries [3]. Although several novel molecular markers and pharmacogenetic studies have been used to intensively investigate complex polygenic chronic or degenerative diseases [4][5][6][7][8][9][10][11][12][13] leading to the discovery of novel prognostic biomarkers or inherited predispositions [14][15][16][17][18][19], specific dedicated therapies to treat heart failure due to heart wall remodeling do not currently exist, and women experience the worst prognosis [1,20,21]. Epidemiological data highlight that CVD now represents the leading cause of mortality and hospital admission for women, accounting for one in three deaths worldwide and half of all deaths of women over 50 in developing countries [3].…”